The development of methods for the detection and quantitation of various isozymes of cytochrome P-450 allows for the determination of isozyme distribution and analysis of expression of activities relative to enzyme content. Although it is known that the turnover numbers for some isozymes decrease following isozyme induction, we have now shown that the extent of the decrease depends upon the substrate examined. Treatment of rabbits with TCDD results in a 20-fold increase in the pulmonary content of cytochrome P-450, isozyme 6. The metabolism of two substrates for isozyme 6 also increases, but to different extents, the 0-deethylation of 7-ethoxyresorufin increases about 10-fold and the hydroxylation of benzo(a)pyrene increases only about l.5-fold. Maximum activity with both substrates is obtained by the addition of purified cytochrome P-450 reductase to the microsomal incubations. The induction of isozyme 6 and the differential expression of activity with benzo(a)-pyrene and 7-ethoxyresorufin is also observed with microsomal preparations from alveolar type II cells, Clara cells and pulmonary macrophages isolated from lungs of rabbits treated with TCDD. The effect of TCDD on the pulmonary cytochrome P-450 systems of species other than rabbit has also been examined. Treatment of rats, mice, guinea pigs and hamsters with TCDD induced a form of cytochrome P-450 related immunochemically to isozyme 6. These isozymes are also detected with antibodies to the rat homolog of isozyme 6, P-450c. Treatment of all species with TCDD results in the increases in the concentrations of two isozymes in liver; the homologs of isozymes 6 and 4. The homolog of isozyme 6 is also detected in placental microsomal fractions from humans exposed to PCBs found in contaminated rice oil.